This study is undertaken to understand the biosynthesis of Vitamin-B12-factors (corrinoids) and the role of these factors and derivatives of tetrahydrofolate in the synthesis of acetate from CO2. The work will be done using Clostridium thermoaceticum and Clostridium formicoaceticum. Potential intermediates in the biosynthesis of corrinoids have been isolated from cells grown in the presence of radioactive delta-aminolevulinic acid. Attempts will be made to identify these compounds and to find if they are intermediates in the corrinoid synthesis. The first enzyme in the formation of acetate from CO2 is formate dehydrogenase. It catalyzes the reduction of CO2 to formate. The formation of this enzyme is stimulated by adding selenite, molybdate and tungstate to the growth medium. The incorporation of these metals into the formate dehydrogenase will be studied and their role in the enzyme reaction. A corrinoid-protein has been isolated from C. thermoaceticum. The role of this protein in the formation of acetate from methyltetrahydrofolate and pyruvate will be investigated. A second corrinoid-protein also present in C. thermoaceticum will be isolated and characterized. The enzyme mechanisms of formyltetrahydrofolate synthetase and methylenetetrahydrofolate reductase from the above clostridia will be investigated.